U.S. patent application number 11/418171 was filed with the patent office on 2007-12-06 for ion guide for mass spectrometers.
Invention is credited to Taeman Kim, Melvin Andrew Park.
Application Number | 20070278399 11/418171 |
Document ID | / |
Family ID | 32850675 |
Filed Date | 2007-12-06 |
United States Patent
Application |
20070278399 |
Kind Code |
A1 |
Kim; Taeman ; et
al. |
December 6, 2007 |
Ion guide for mass spectrometers
Abstract
The present invention relates generally to mass spectrometry and
the analysis of chemical samples, and more particularly to ion
guides for use therein. The invention described herein comprises an
improved method and apparatus for transporting ions from a first
pressure region in a mass spectrometer to a second pressure region
therein. More specifically, the present invention provides a
segmented ion funnel for more efficient use in mass spectrometry
(particularly with ionization sources) to transportions from the
first pressure region to the second pressure region.
Inventors: |
Kim; Taeman; (North
Billerica, MA) ; Park; Melvin Andrew; (Billerica,
MA) |
Correspondence
Address: |
WARD & OLIVO
SUITE 300
382 SPRINGFIELD AVENUE
SUMMIT
NJ
07901
US
|
Family ID: |
32850675 |
Appl. No.: |
11/418171 |
Filed: |
May 4, 2006 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10407860 |
Apr 4, 2003 |
|
|
|
11418171 |
May 4, 2006 |
|
|
|
Current U.S.
Class: |
250/288 ;
250/281 |
Current CPC
Class: |
H01J 49/066
20130101 |
Class at
Publication: |
250/288 ;
250/281 |
International
Class: |
H01J 3/14 20060101
H01J003/14 |
Claims
1.-145. (canceled)
146. An ion guide for use in a mass spectrometer, said ion guide
comprising: a first set of apertured electrodes having a first
potential applied thereto; a second set of apertured electrodes
having a second potential applied thereto; first and second power
sources for generating said first and second potentials,
respectively, said power sources applying said potentials such that
said ions may be selectively trapped in said ion guide or
transmitted through said ion guide; and first and second apertured
lens elements positioned at either end of said ion guide; wherein
ions are introduced into an entrance end of said ion guide through
said first lens element, and wherein each electrode of said first
set of electrodes is positioned between two electrodes of said
second set of electrodes.
147. An ion guide according to claim 145, wherein said first
potential is a substantially RF-only potential.
148. An ion guide according to claim 145, wherein said second
potential is a substantially DC-only potential.
149. An ion guide according to claim 145, wherein said first and
second electrodes are aligned along a common axis.
150. An ion guide according to claim 149, wherein said ions are
produced from an ion source positioned orthogonal to said common
axis.
151. An ion guide according to claim 145, wherein at least one
electrode of said first electrodes comprises alternating
electrically insulating and electrically conducting regions.
152. An ion guide according to claim 145, wherein said first
potential is a sinusoidally time-varying potential.
153. An ion guide according to claim 152, wherein said first
potential applied to one of said first electrodes is 180.degree.
out of phase with said first potential applied to each adjacent
said first electrode.
154. An ion guide according to claim 145, wherein said first and
second potentials have a non-zero reference potential.
155. An ion guide according to claim 145, wherein said lens
elements are maintained at a DC potential greater than said second
potential.
156. An ion guide according to claim 145, wherein said ion guide
begins in a region having a first pressure and ends in a region
having a second pressure.
157. An ion guide according to claim 145, wherein said first and
second potentials are applied via at least one network of resistors
and capacitors.
158. An ion guide according to claim 157, wherein said network of
resistors and capacitors is configured such that substantially
RF-only potentials are applied to said first electrodes through
said capacitors.
159. An ion guide according to claim 157, wherein said network of
resistors and capacitors is configured such that electrostatic
potentials are applied to said second electrodes through said
resistors.
160. A method for analyzing a chemical sample, said method
comprising the steps of: generating ions from a sample; introducing
said ions into a first pressure region of a mass spectrometer;
directing said ions into through a first lens element into an ion
guide comprising a plurality of first and second apertured
electrodes, wherein each electrode of said first set of electrodes
is positioned between two electrodes of said second set of
electrodes; applying first and second potentials to said first and
second electrodes via first and second power sources such that said
ions are transmitted from a first pressure region into a second
pressure region; and transmitting said ions from said second
pressure region into a mass analyzer for subsequent analysis.
161. A method according to claim 160, wherein an electrostatic
potential is applied to said second apertured electrodes as a
function of said second apertured electrodes position along a
common axis of said ion guide such that said electrostatic
potential most repulsive to said ions is applied to said second
electrodes at an entrance end of said ion guide and said
electrostatic potential most attractive to said ions is applied to
said second electrodes at an exit end of said ion guide.
162. A method according to claim 160, wherein said ions are
produced from an ion source positioned orthogonal to said common
axis.
163. A method according to claim 160, wherein said first and second
potentials are applied via at least one network of resistors and
capacitors.
164. A method according to claim 163, wherein said network of
resistors and capacitors is configured such that substantially
RF-only potentials are applied to said first electrodes through
said capacitors.
165. A method according to claim 164, wherein said substantially
RF-only potentials applied to one of said first electrodes is
180.degree. out of phase with said substantially RF-only potential
applied to each adjacent said first electrode.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 10/407,860, which is incorporated in its entirety herein
by reference.
TECHNICAL FIELD OF THE INVENTION
[0002] The present invention generally relates to an improved
method and apparatus for the injection of ions into a mass
spectrometer for subsequent analysis. Specifically, the invention
relates to an apparatus for use with an ion source that facilitate
the transmission of ions from an elevated pressure ion production
region to a reduced pressure ion analysis region of a mass
spectrometer. A preferred embodiment of the present invention
allows for improved efficiency in the transmission of ions from a
relatively high pressure region, through a multitude of
differential pumping stages, to a mass analyzer.
BACKGROUND OF THE INVENTION
[0003] The present invention relates to ion guides for use in mass
spectrometry. The apparatus and methods for ionization described
herein are enhancements of the techniques referred to in the
literature relating to mass spectrometry--an important tool in the
analysis of a wide range of chemical compounds. Specifically, mass
spectrometers can be used to determine the molecular weight of
sample compounds. The analysis of samples by mass spectrometry
consists of three main steps--formation of gas phase ions from
sample material, mass analysis of the ions to separate the ions
from one another according to ion mass, and detection of the ions.
A variety of means and methods exist in the field of mass
spectrometry to perform each of these three functions. The
particular combination of the means and methods used in a given
mass spectrometer determine the characteristics of that
instrument.
[0004] To mass analyze ions, for example, one might use magnetic
(B) or electrostatic (E) analysis, wherein ions passing through a
magnetic or electrostatic field will follow a curved path. In a
magnetic field, the curvature of the path will be indicative of the
momentum-to-charge ratio of the ion. In an electrostatic field, the
curvature of the path will be indicative of the energy-to-charge
ratio of the ion. If magnetic and electrostatic analyzers are used
consecutively, then both the momentum-to-charge and
energy-to-charge ratios of the ions will be known and the mass of
the ion will thereby be determined. Other mass analyzers are the
quadrupole (Q), the ion cyclotron resonance (ICR), the
time-of-flight (TOF), and the quadrupole ion trap analyzers. The
analyzer which accepts ions from the ion guide described here may
be any of a variety of these.
[0005] Before mass analysis can begin, gas phase ions must be
formed from a sample material. If the sample material is
sufficiently volatile, ions may be formed by electron ionization
(EI) or chemical ionization (CI) of the gas phase sample molecules.
Alternatively, for solid samples (e.g., semiconductors, or
crystallized materials), ions can be formed by desorption and
ionization of sample molecules by bombardment with high energy
particles. Further, Secondary Ion Mass Spectrometry (SIMS), for
example, uses keV ions to desorb and ionize sample material. In the
SIMS process a large amount of energy is deposited in the analyte
molecules, resulting in the fragmentation of fragile molecules.
This fragmentation is undesirable in that information regarding the
original composition of the sample (e.g., the molecular weight of
sample molecules) will be lost.
[0006] For more labile, fragile molecules, other ionization methods
now exist. The plasma desorption (PD) technique was introduced by
Macfarlane et al. (R. D. Macfarlane, R. P. Skowronski, D. F.
Torgerson, Biochem. Biophys. Res Commoun. 60 (1974)
616)("McFarlane"). Macfarlane discovered that the impact of high
energy (MeV) ions on a surface, like SIMS would cause desorption
and ionization of small analyte molecules. However, unlike SIMS,
the PD process also results in the desorption of larger, more
labile species (e.g., insulin and other protein molecules).
[0007] Additionally, lasers have been used in a similar manner to
induce desorption of biological or other labile molecules. See, for
example, Cotter et al. (R. B. VanBreeman, M. Snow, R. J. Cotter,
Int. J. Mass Spectrom. Ion Phys. 49 (1983) 35; Tabet, J. C.;
Cotter, R. J., Tabet, J. C., Anal. Chem. 56 (1984) 1662; or R. J.
Cotter, P. Demirev, I. Lys, J. K. Olthoff, J. K.; Lys, I.: Demirev,
P.: Cotter et al., R. J., Anal. Instrument. 16 (1987) 93). Cotter
modified a CVC 2000 time-of-flight mass spectrometer for infrared
laser desorption of involatile biomolecules, using a Tachisto
(Needham, Mass.) model 215G pulsed carbon dioxide laser. The plasma
or laser desorption and ionization of labile molecules relies on
the deposition of little or no energy in the analyte molecules of
interest. The use of lasers to desorb and ionize labile molecules
intact was enhanced by the introduction of matrix assisted laser
desorption ionization (MALDI) (K. Tanaka, H. Waki, Y. Ido, S.
Akita, Y. Yoshida, T. Yoshica, Rapid Commun. Mass Spectrom. 2
(1988) 151 and M. Karas, F. Hillenkamp, Anal. Chem. 60 (1988)
2299). In the MALDI process, an analyte is dissolved in a solid,
organic matrix. Laser light of a wavelength that is absorbed by the
solid matrix but not by the analyte is used to excite the sample.
Thus, the matrix is excited directly by the laser, and the excited
matrix sublimes into the gas phase carrying with it the analyte
molecules. The analyte molecules are then ionized by proton,
electron, or cation transfer from the matrix molecules to the
analyte molecules. This process (i.e., MALDI) is typically used in
conjunction with time-of-flight mass spectrometry (TOFMS) and can
be used to measure the molecular weights of proteins in excess of
100,000 daltons.
[0008] Further, Atmospheric Pressure Ionization (API) includes a
number of ion production means and methods. Typically, analyte ions
are produced from liquid solution at atmospheric pressure. One of
the more widely used methods, known as electrospray ionization
(ESI), was first suggested by Dole et al. (M. Dole, L. L. Mack, R.
L. Hines, R. C. Mobley, L. D. Ferguson, M. B. Alice, J. Chem. Phys.
49, 2240, 1968). In the electrospray technique, analyte is
dissolved in a liquid solution and sprayed from a needle. The spray
is induced by the application of a potential difference between the
needle and a counter electrode. The spray results in the formation
of fine, charged droplets of solution containing analyte molecules.
In the gas phase, the solvent evaporates leaving behind charged,
gas phase, analyte ions. This method allows for very large ions to
be formed. Ions as large as 1 MDa have been detected by ESI in
conjunction with mass spectrometry (ESMS).
[0009] In addition to ESI, many other ion production methods might
be used at atmospheric or elevated pressure. For example, MALDI has
recently been adapted by Laiko et al. to work at atmospheric
pressure (Victor Laiko and Alma Burlingame, "Atmospheric Pressure
Matrix Assisted Laser Desorption", U.S. Pat. No. 5,965,884, and
Atmospheric Pressure Matrix Assisted Laser Desorption Ionization,
poster #1121, 4.sup.th International Symposium on Mass Spectrometry
in the Health and Life Sciences, San Francisco, Aug. 25-29, 1998)
and by Standing et al. at elevated pressures (Time of Flight Mass
Spectrometry of Biomolecules with Orthogonal Injection+Collisional
Cooling, poster #1272, 4.sup.th International Symposium on Mass
Spectrometry in the Health and Life Sciences, San Francisco, Aug.
25-29, 1998; and Orthogonal Injection TOFMS Anal. Chem. 71(13),
452A (1999)). The benefit of adapting ion sources in this manner is
that the ion optics (i.e., the electrode structure and operation)
in the mass analyzer and mass spectral results obtained are largely
independent of the ion production method used.
[0010] The elevated pressure MALDI source disclosed by Standing
differs from what is disclosed by Laiko et al. Specifically, Laiko
et al. disclose a source intended to operate at substantially
atmospheric pressure. In contrast, as depicted in FIG. 1, the
source 1 disclosed by Standing et al. is intended to operate at a
pressure of about 70 mtorr. In addition, as shown in FIG. 1, the
MALDI sample resides on the tip 6 of a MALDI probe 2 in the second
pumping stage 3 immediately in front of the first of two quadrupole
ion guides 4. Using a laser 7, ions are desorbed from the MALDI
sample directly into 70 mTorr of gas and are immediately drawn into
the ion guides 4 by the application of an electrostatic field. Even
though this approach requires that one insert the sample into the
vacuum system, it has the advantage of improved ion transmission
efficiency over that of the Laiko source. That is, the possible
loss of ions during transmission from the elevated pressure source
1, operated at atmospheric pressure, to the third pumping region
and the ion guide therein is avoided because the ions are generated
directly in the second pumping stage.
[0011] Elevated pressure (i.e., elevated relative to the pressure
of the mass analyzer) and atmospheric pressure ion sources always
have an ion production region, wherein ions are produced, and an
ion transfer region, wherein ions are transferred through
differential pumping stages and into the mass analyzer. Generally,
mass analyzers operate in a vacuum between 10.sup.-4 and 10.sup.-10
torr depending on the type of mass analyzer used. When using, for
example, an ESI or elevated pressure MALDI source, ions are formed
and initially reside in a high pressure region of "carrier" gas. In
order for the gas phase ions to enter the mass analyzer, the ions
must be separated from the carrier gas and transported through the
single or multiple vacuum stages.
[0012] As a result, the use of multipole ion guides has been shown
to be an effective means of transporting ions through a vacuum
system. Publications by Olivers et al. (Anal. Chem, Vol. 59, p.
1230-1232, 1987), Smith et al. (Anal. Chem. Vol. 60, p. 436-441,
1988) and Douglas et al. (U.S. Pat. No. 4,963,736) have reported
the use of AC-only quadrupole ion guides to transportions from an
API source to a mass analyzer.
[0013] In the prior art, according to Douglas et al., as depicted
in FIG. 2, ionization chamber 17 is connected to curtain gas
chamber 24 via opening 18 in curtain gas plate 23. Curtain gas
chamber 24 is connected by orifice 25 of orifice plate 29 to first
vacuum chamber 44 that is pumped by vacuum pump 31. Vacuum chamber
44 contains a set of four AC-only quadrupole mass spectrometer rods
33. Also, the vacuum chamber 44 is connected by interchamber
orifice 35 in separator plate 37 to a second vacuum chamber 51
pumped by vacuum pump 39. Chamber 51 contains a set of four
standard quadrupole mass spectrometer rods 41.
[0014] An inert curtain gas, such as nitrogen, argon or carbon
dioxide, is supplied via a curtain gas source 43 and duct 45 to the
curtain gas chamber 24. (Dry air may also be used in some cases.)
The curtain gas flows through orifice 25 into the first vacuum
chamber 44 and also flows into the ionization chamber 17 to prevent
air and contaminants in chamber 17 from entering the vacuum system.
Excess sample, and curtain gas, leave the ionization chamber 17 via
outlet 47.
[0015] Ions produced in the ionization chamber 17 are drifted by
appropriate DC potentials on plates 23 and 29 and on the AC-only
rod set 33 through opening 18 and orifice 25, and then are guided
through the AC-only rod set 33 and interchamber orifice 35 into the
rod set 41. An AC RF voltage (typically at a frequency of about 1
Megahertz) is applied between the rods of rod set 33, as is well
known, to permit rod set 33 to perform its guiding and focusing
function. Both DC and AC RF voltages are applied between the rods
of rod set 41, so that rod set 41 performs its normal function as a
mass filter, allowing only ions of selected mass to charge ratio to
pass therethrough for detection by ion detector 49.
[0016] Douglas et al. found that under appropriate operating
conditions, an increase in the gas pressure in the first vacuum
chamber 44 not only failed to cause a decrease in the ion signal
transmitted through orifice 35, but in fact most unexpectedly
caused a considerable increase in the transmitted ion signal. In
addition, under appropriate operating conditions, it was found that
the energy spread of the transmitted ions was substantially
reduced, thereby greatly improving the ease of analysis of the
transmitted ion signal. The particular "appropriate operating
conditions" disclosed by Douglas et al. maintain the second vacuum
chamber 51 at low pressure (e.g. 0.02 millitorr or less) but the
product of the pressure in the first chamber 44 and the length of
the AC-only rods 33 is held above 2.25.times.10.sup.-2 torr-cm,
preferably between 6.times.10.sup.-2 and 15.times.10.sup.-2
torr-cm, and the DC voltage between the inlet plate 29 and the
AC-only rods 33 is kept low (e.g., between 1 and 30 volts)
preferably between 1 and 10 volts.
[0017] As shown in FIG. 3, mass spectrometers similar to that of
Whitehouse et al. ("Multipole Ion Guide for Mass Spectrometry",
U.S. Pat. No. 5,652,427) use multipole RF ion guides 42 to transfer
ions from one pressure region 30 to another 34 in a differentially
pumped system. In this ion source, ions are produced by ESI or APCI
at substantially atmospheric pressure. These ions are transferred
from atmospheric pressure to a first differential pumping region by
the gas flow through a glass capillary 60. Further, ions are
transferred from this first pumping region 30 to a second pumping
region 32 through a "skimmer" 56 by gas flow as well as an electric
field present between these regions. Multipole ion guide 42 in the
second differentially pumped region 32 accepts ions of a selected
mass/charge (m/z) ratio and guides them through a restriction and
into a third differentially pumped region 34 by applying AC and DC
voltages to the individual poles of the ion guide 42.
[0018] Further, as depicted in FIG. 3, a four vacuum stage
ESI-reflectron-TOF mass spectrometer, according to Whitehouse et
al., incorporates a multipole ion guide 42 beginning in one vacuum
pumping stage 32 and extending contiguously into an adjacent
pumping stage 34. As shown here, ions are formed from sample
solution by an electrospray process. Sample bearing liquid is
introduced through the electrospray needle 26 and is electrosprayed
or nebulization-assisted electrosprayed into chamber 28 as it exits
the needle tip 27 producing charged droplets. The charged droplets
evaporate and desorb gas phase ions both in chamber 28 and as they
are swept into the vacuum system through the annulus 38 in
capillary 60. According to the prior art system shown in FIG. 3,
capillary 60 is used to transportions from chamber 28, where the
ions are formed, to first pumping region 30. A portion of the ions
that enter the first vacuum stage 30 through the capillary exit 40
are focused through the orifice 58 in skimmer 56 with the help of
lens 62 and the potential set on the capillary exit 40. Ions
passing through orifice 58 enter the multipole ion guide 42, which
begins in vacuum pumping stage 32 and extends unbroken into vacuum
stage 34. According to Whitehouse et al. the RF only ion guide 42
is a hexapole. The electrode rods of such prior art multipole ion
guides are positioned parallel and are equally spaced at a common
radius from the centerline of the ion guide. A high voltage RF
potential is applied to the electrode rods of the ion guide so as
to push the ions toward the centerline of the ion guide. Ions with
a m/z ratio that fall within the ion guide stability window
established by the applied voltages have stable trajectories within
the ion guide's internal volume bounded by the evenly-spaced,
parallel rods. This is true for quadrupoles, hexapoles, octapoles,
or any other multipole used to guide ions. As previously disclosed
by Douglas et al., operating the ion guide in an appropriate
pressure range results in improved ion transmission efficiency.
[0019] Whitehouse et al. further disclose that collisions with the
gas reduces the ion kinetic energy to that of the gas (i.e., room
temperature). This hexapole ion guide 42 is intended to provide for
the efficient transport of ions from one location (i.e., the
entrance 58 of skimmer 56) to a second location (i.e., orifice 50).
Of particular note is that a single contiguous multipole 42 resides
in more than one differential pumping stage and guides ions through
the pumping restriction between them. Compared to other prior art
designs, this offers improved ion transmission through pumping
restrictions.
[0020] If the multipole ion guide AC and DC voltages are set to
pass ions falling within a range of m/z then ions within that range
that enter the multipole ion guide 42 will exit at 46 and be
focused with exit lens 48 through the TOF analyzer entrance orifice
50. The primary ion beam 82 passes between electrostatic lenses 64
and 68 that are located in the fourth pumping stage 36. The
relative voltages on lenses 64, 68 and 70 are pulsed so that a
portion of the ion beam 82 falling in between lenses 64 and 68 is
ejected as a packet through grid lens 70 and accelerated down
flight tube 80. The ions are steered by x and y lens sets
diagrammatically illustrated by 72 as they continue moving down
flight tube 80. As shown in this illustrative configuration, the
ion packet is reflected through a reflectron or ion mirror 78,
steered again by x and y lens sets illustrated by 76 and detected
at detector 74. As a pulsed ion packet proceeds down flight tube
80, ions with different m/z separate in space due to their velocity
differences and arrive at the detector at different times.
Moreover, the use of orthogonal pulsing in an API/TOF system helps
to reduce the ion energy spread of the initial ion packet allowing
for the achievement of higher resolution and sensitivity.
[0021] In U.S. Pat. No. 6,011,259 Whitehouse et al. also disclose
trapping ions in a multipole ion guide and subsequently releasing
them to a TOF mass analyzer. In addition, Whitehouse et al.
disclose ion selection in such a multipole ion guide, collision
induced dissociation of selected ions, and release of the fragment
ions thus produced to the TOF mass analyzer. Further, the use of
two or more ion guides in consecutive vacuum pumping stages
allowing for different DC and RF values is also disclosed by
Whitehouse et al. However, losses in ion transmission efficiency
may occur in the region of static voltage lenses between ion
guides. For example, a commercially available API/MS instrument
manufactured by Hewlett Packard incorporates two skimmers and an
ion guide. An interstage port (also called a drag stage port) is
used to pump the region between the skimmers. That is, an
additional pumping stage/region is added without the addition of an
extra turbo pump, thereby improving pumping efficiency. In this
dual skimmer design, there is no ion focusing device between
skimmers, therefore ion losses may occur as the gases are pumped
away. A second example is demonstrated by a commercially available
API/MS instrument manufactured by Finnigan which applies an
electrostatic lens between capillary and skimmer to focus the ion
beam. Due to a narrow mass range of the static lens, the instrument
may need to scan the voltage to optimize the ion transmission.
[0022] According to Thomson et al. (entitled "Quadrupole with Axial
DC Field", U.S. Pat. No. 6,111,250), a quadrupole mass spectrometer
contains four rod sets, referred to as Q0, Q1, Q2 and Q3. A rod set
is constructed to create an axial field (e.g., a DC axial field)
thereon. The axial field can be created by tapering the rods, or
arranging the rods at angles with respect to each other, or
segmenting the rods as depicted in FIG. 4. When the axial field is
applied to Q0 in a tandem quadrupole set, it speeds passage of ions
through Q0 and reduces delay caused by the need to refill Q0 with
ions when jumping from low to high mass in Q1. When used as
collision cell Q2, the axial field reduces the delay needed for
daughter ions to drain out of Q2. The axial field can also be used
to help dissociate ions in Q2, either by driving the ions forwardly
against the collision gas, or by oscillating the ions axially
within the collision cell.
[0023] One such prior art device disclosed by Thomson et al. is
depicted in FIG. 4, which shows a quadrupole rod set 96 consisting
of two pair of parallel cylindrical rod sets 96A and 96B arranged
in the usual fashion but divided longitudinally into six segments
96A-1 to 96A-6 and 96B-1 to 96B-6. The gap 98 between adjacent
segments or sections is very small (e.g., about 0.5 mm). Each A
section and each B section is supplied with the same RF voltage
from RF generator, via isolating capacitors C3, but each is
supplied with a different DC voltage V1 to V6 via resistors R1 to
R6. Thus, sections 96A-1, 96B-1 receive voltage V1, sections 96A-2,
96B-2 receive voltage V2, and so on. This produces a stepped
voltage along the central longitudinal axis 100 of the rod set 96.
Connection of the R-C network and thus the voltage applied to
sections 96B-1 to 96B-6 are not separately shown. The separate
potentials can be generated by separate DC power supplies for each
section or by one power supply with a resistive divider network to
supply each section. The step wise potential produces an
approximately constant axial field. While more sections over the
same length will produce a finer step size and a closer
approximation to a linear axial field, it is found that using six
sections as shown produces good results.
[0024] For example, such a segmented quadrupole was used to
transmit ions from an atmospheric pressure ion source into a
downstream mass analyzer. The pressure in the quadrupole was 8.0
millitorr. Thomson et al. found that at high pressure without an
axial field the ions of a normal RF quadrupole at high pressure
without an axial field can require several tens of milliseconds to
reach a steady state signal. However, with the use of an axial
field that keeps the ions moving through the segmented quadrupole,
the recovery or fill-up time of segmented quadrupoles, after a
large change in RF voltage, is much shorter.
[0025] In a similar manner Wilcox et al. (B. E. Wilcox, J. P.
Quinn, M. R. Emmett, C. L. Hendrickson, and A. Marshall,
Proceedings of the 50.sup.th ASMS Conference on Mass Spectrometry
and Allied Topics, Orlando, Fla., Jun. 2-6, 2002) demonstrated the
use of a pulsed electric field to eject ions from an octapole ion
guide. Wilcox et al. found that the axial electric field caused
ions in the octapole to be ejected more quickly. This resulted in
an increase in the effective efficiency of transfer of ions from
the octapole to their mass analyzer by as much as a factor of
14.
[0026] Another type of prior art ion guide, depicted in FIG. 5, is
disclosed by Franzen et al. in U.S. Pat. No. 5,572,035, entitled
"Method and Device for the Reflection of Charged Particles on
Surfaces". According to Franzen et al., the ion guide 11 comprises
a series of parallel rings 12, each ring having a phase opposite
that of its two neighboring rings. Thus, along the axis there
exists a slightly undulating structure of the pseudo potential,
slightly obstructive for a good and smooth guidance of ions. On the
other hand, the diffuse reflection of particles at the cylinder
wall is favorable for a fast thermalization of the ion's kinetic
energy if the ions are shot about axially into the cylinder. This
arrangement generates, in each of the ring centers, the well-known
potential distribution of ion traps with their characteristic
equipotential surfaces crossing in the center with angles of
.alpha.=2arctan(1/2.sup.0.5). The quadrupole fields, however, are
restricted to very small areas around each center. In the direction
of the cylinder axis, the pseudo potential wells of the centers are
shallow because the traps follow each other in narrow sequence. In
general, the pseudo potential wells are less deep the closer the
rings are together. Emptying this type of ion guide by simply
letting the ions flow out leaves some ions behind in the shallow
wells.
[0027] In this prior art ion guide according to Franzen, an axial
DC field is used to drive the ions out, ensuring that the ion guide
is completely emptied. The electric circuits needed to generate
this DC field are shown in FIG. 5. As shown, the RF voltage is
supplied to the ring electrodes 12 via condensers, and the rings
are connected by a series of resistance chokes 14 forming a
resistive voltage divider for the DC voltage, and hindering the RF
from flowing through the voltage divider. The DC current is
switchable, and the DC field helps to empty the device of any
stored ions. With rings 12 being approximately five millimeters in
diameter, resistance chokes 14 of 10 microhenries and 100 Ohms, and
capacitors 16 of 100 picofarads build up the desired DC fields.
Fields of a few volts per centimeter are sufficient.
[0028] A similar means for guiding ions at "near atmospheric"
pressures (i.e., pressures between 10.sup.-1 millibar and 1 bar) is
disclosed by Smith et al. in U.S. Pat. No. 6,107,628, entitled
"Method and Apparatus for Directing Ions and Other Charged
Particles Generated at Near Atmospheric Pressures into a Region
Under Vacuum". One embodiment, illustrated in FIG. 6, consists of a
plurality of elements, or rings 13, each element having an
aperture, defined by the ring inner surface 20. At some location in
the series of elements, each adjacent aperture has a smaller
diameter than the previous aperture, the aggregate of the apertures
thus forming a "funnel" shape, otherwise known as an ion funnel.
The ion funnel thus has an entry, corresponding with the largest
aperture 21, and an exit, corresponding with the smallest aperture
22. According to Smith et al., the rings 13 containing apertures 20
may be formed of any sufficiently conducting material. Preferably,
the apertures are formed as a series of conducting rings, each ring
having an aperture smaller than the aperture of the previous ring.
Further, an RF voltage is applied to each of the successive
elements so that the RF voltages of each successive element is 180
degrees out of phase with the adjacent element(s), although other
relationships for the applied RF field would likely be appropriate.
Under this embodiment, a DC electrical field is created using a
power supply and a resistor chain to supply the desired and
sufficient voltage to each element to create the desired net motion
of ions through the funnel.
[0029] Each of the ion guide devices mentioned above in the prior
art have their own particular advantages and disadvantages. For
example, the "ion funnel" disclosed by Smith et al. has the
advantage that it can efficiently transmit ions through a
relatively high pressure region (i.e., >0.1 mbar) of a vacuum
system, whereas multipole ion guides perform poorly at such
pressures. However, the ion funnel disclosed by Smith et al.
performs poorly at lower pressures where multipole ion guides
transmit ions efficiently. In addition, this ion funnel has a
narrow range of effective geometries. That is, the thickness of the
plates and the gap between the plates must be relatively small
compared to the size of the aperture in the plate. Otherwise, ions
may get trapped in electrodynamic "wells" in the funnel and
therefore not be efficiently transmitted.
[0030] Similarly, the ion guide disclosed by Franzen et al. and
shown in FIG. 5 must have apertures which are large relative to
plate thickness and gap. Also while Franzen et al's ion guide can
have an "axial" DC electric field to push the ions towards the
exit, the DC field cannot be changed rapidly or switched on or off
quickly. That is, the speed with which the DC field is switched
must be much slower than that represented by the frequency of the
RF potential applied to confine the ions. Similarly, the segmented
quadrupole of Thomson et al. allows for an axial DC electric field.
However, in Thomson et al., the field cannot be rapidly
switched.
[0031] As discussed below, the ion guide according to the present
invention overcomes many of the limitations of prior art ion
guides. The ion guide disclosed herein provides a unique
combination of attributes making it more suitable for use in the
transport of ions from high pressure ion production regions to low
pressure mass analyzers.
SUMMARY OF THE INVENTION
[0032] The present invention relates generally to mass spectrometry
and the analysis of chemical samples, and more particularly to ion
guides for use therein. The invention described herein comprises an
improved method and apparatus for transporting ions from a first
pressure region in a mass spectrometer to a second pressure region
therein. More specifically, the present invention provides a
segmented ion funnel for more efficient use in mass spectrometry,
particularly with ionization sources, to transportions from the
first pressure region to a second pressure region.
[0033] In light of the above described inadequacies in the prior
art, a primary aspect of the present invention is to provide a
means and method for efficiently guiding ions in and through high
(i.e., >=0.1 mbar) and low (i.e., <=0.1 mbar) pressure
regions of a mass spectrometer. Whereas, some prior art devices
function well at high pressures and other devices function well at
low pressures, the ion guide according to the present invention
functions efficiently at both high and low pressures. It is
therefore also considered another aspect of the present invention
to provide an ion funnel device which begins in one pumping region
and ends in another pumping region and guides ions through a
pumping restriction between the two regions. The first of said
pumping regions may be a relatively high pressure (i.e., >0.1
mbar) region whereas subsequent pumping regions are lower
pressure.
[0034] It is another aspect of the present invention to provide a
means and method for rapidly ejecting ions from an ion guide. Ions
may initially be trapped, for example in a stacked ring ion guide,
and then ejected from the guide as a pulse of ions. Ejection is
effected by applying a pulsed electric potential to "DC electrodes"
so as to force ions towards the exit end of the ion guide. Ions
might be ejected into a mass analyzer or into some other
device--e.g. a collision cell.
[0035] It is yet a further aspect of the present invention to
provide a means and method for performing tandem mass spectrometry
experiments. Particularly, a device according to the present
invention might be used as a "collision cell" as well as an ion
guide. When used in combination with an upstream mass analyzer,
selected ions can be caused to form fragment ions. Further, a
"downstream" mass analyzer may be used to analyze fragment ions
thus formed. Therefore in combination with appropriate mass
analyzers a fragment ion (or MS/MS) spectrum can be obtained.
Alternatively, as discussed by Hofstadler et al. ("Methods and
Apparatus for External Accumulation and Photodissociation of Ions
Prior to Mass Spectrometric Analysis", U.S. Pat. No. 6,342,393) the
ion guide might operate at a predetermined pressure such that ions
in the guide can be irradiated with light and thereby caused to
form fragment ions for subsequent mass analysis.
[0036] It is yet a further aspect of the present invention to
provide a means and method for accepting and guiding ions from a
multitude of ion production means. As described above, a number of
means and methods for producing ion are known in the prior art. An
ion guide according to the present invention may accept ions
simultaneously from more than one such ion production means. For
example, an elevated pressure MALDI ion production means may be
used in combination with an ESI or other API ion production means
to accept ions either simultaneously or consecutively. Importantly,
the ion production means need not be physically exchanged in order
to switch between them. That is, for example, one need not dismount
the MALDI means and mount an ESI means in its place to switch from
MALDI to ESI.
[0037] Other objects, features, and characteristics of the present
invention, as well as the methods of operation and functions of the
related elements of the structure, and the combination of parts and
economies of manufacture, will become more apparent upon
consideration of the following detailed description with reference
to the accompanying drawings, all of which form a part of this
specification.
BRIEF DESCRIPTION OF THE DRAWINGS
[0038] A further understanding of the present invention can be
obtained by reference to a preferred embodiment set forth in the
illustrations of the accompanying drawings. Although the
illustrated embodiment is merely exemplary of systems for carrying
out the present invention, both the organization and method of
operation of the invention, in general, together with further
objectives and advantages thereof, may be more easily understood by
reference to the drawings and the following description. The
drawings are not intended to limit the scope of this invention,
which is set forth with particularity in the claims as appended or
as subsequently amended, but merely to clarify and exemplify the
invention.
[0039] For a more complete understanding of the present invention,
reference is now made to the following drawings in which:
[0040] FIG. 1 shows an elevated pressure MALDI source according to
Standing et al.;
[0041] FIG. 2 depicts a prior art ion guide according to Douglas et
al.;
[0042] FIG. 3 depicts a prior art mass spectrometer according to
Whitehouse et al., including an ion guide for transmitting ions
across differential pumping stages;
[0043] FIG. 4 is a diagram of a prior art segmented multipole
according to Thomson et al.;
[0044] FIG. 5 shows a prior art "stacked ring" ion guide according
to Franzen et al.;
[0045] FIG. 6 depicts a prior art "ion funnel" guide according to
Smith et al.;
[0046] FIG. 7A depicts a "segmented" electrode ring according to
the present invention which, in this example, includes four
electrically conducting segments;
[0047] FIG. 7B is a cross-sectional view of the segmented electrode
of FIG. 7A formed at line A-A;
[0048] FIG. 7C is a cross-sectional view of the segmented electrode
of FIG. 7A formed at line B-B;
[0049] FIG. 7D depicts a "segmented" electrode ring according to
the present invention which, in this example, includes six
electrically conducting segments;
[0050] FIG. 7E is a cross-sectional view of the segmented electrode
of FIG. 7D formed at line A-A;
[0051] FIG. 7F is a cross-sectional view of the segmented electrode
of FIG. 7D formed at line B-B;
[0052] FIG. 8A depicts an end view of a "segmented" funnel
according to the present invention constructed from segmented
electrodes of the type shown in FIG. 7A;
[0053] FIG. 8B is a cross-sectional view of the segmented funnel of
FIG. 8A formed at line A-A;
[0054] FIG. 9A shows a cross-sectional view of the segmented funnel
of FIG. 8A formed at line A-A with the preferred corresponding
electrical connections;
[0055] FIG. 9B shows a cross-sectional view of the segmented funnel
of FIG. 8A formed at line B-B with the preferred corresponding
electrical connections;
[0056] FIG. 10A shows an end view of a segmented funnel according
to the present invention, including a DC lens element at its outlet
end;
[0057] FIG. 10B shows a cross-sectional view of the segmented
funnel of FIG. 10A formed at line A-A;
[0058] FIG. 11 depicts the segmented ion funnel of FIG. 10 in a
vacuum system of a mass spectrometer, including "downstream"
multipole ion guides;
[0059] FIG. 12 is a cross-sectional view of a two-stage segmented
ion funnel;
[0060] FIG. 13 depicts the two-stage segmented ion funnel of FIG.
12 in a vacuum system of a mass spectrometer, including a
"downstream" multipole ion guide;
[0061] FIG. 14 shows a cross-sectional view of a "stacked ring" ion
guide according to an alternative embodiment of the present
invention, including "DC electrodes" interleaved with RF guide
rings;
[0062] FIG. 15 is a plot of electric potential vs. position within
the "stacked ring" ion guide shown in FIG. 14;
[0063] FIG. 16 depicts a cross-sectional view of an alternative
embodiment of the ion guide according to the present invention
comprising features of both the funnel and the stacked ring ion
guides shown in FIGS. 8A-B and 14, respectively;
[0064] FIG. 17 is a plot of electric potential vs. position within
the "funnel/stacked ring" ion guide shown in FIG. 16;
[0065] FIG. 18 depicts a cross-sectional view of a two-stage ion
funnel and "funnel/stacked ring" ion guide in a vacuum system of a
mass spectrometer;
[0066] FIG. 19A shows a first cross-sectional view of the
electrical connections to the "funnel/stacked ring" ion guide shown
in FIG. 18;
[0067] FIG. 19B is a second cross-sectional view, orthogonal to
that of FIG. 19A, of the electrical connection to the
"funnel/stacked ring" ion guide shown in FIG. 18;
[0068] FIG. 20 depicts a cross-sectional view of an alternate
configuration of the "funnel/stacked ring" ion guide of the present
invention comprising multipoles placed between a two-stage
segmented funnel ion guide and a funnel/stacked ring ion
guides;
[0069] FIG. 21 is a plot of electric potential vs. position within
the "funnel/stacked ring" ion guide according to the present
invention with forward and reverse biasing;
[0070] FIG. 22 depicts a cross-sectional view of a two-stage ion
funnel and "funnel/stacked ring" ion guide in a system according to
the present invention wherein the inlet orifice is oriented so as
to introduce ions orthogonally into an ion guide; and
[0071] FIG. 23 shows the system according to the present invention
as depicted in FIG. 22 wherein the deflection plate is used as a
sample carrier for a MALDI ion production means.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
[0072] As required, a detailed illustrative embodiment of the
present invention is disclosed herein. However, techniques, systems
and operating structures in accordance with the present invention
may be embodied in a wide variety of sizes, shapes, forms and
modes, some of which may be quite different from those in the
disclosed embodiment. Consequently, the specific structural and
functional details disclosed herein are merely representative, yet
in that regard, they are deemed to afford the best embodiment for
purposes of disclosure and to provide a basis for the claims herein
which define the scope of the present invention.
[0073] The following presents a detailed description of a preferred
embodiment of the present invention, as well as some alternate
embodiments of the invention. As discussed above, the present
invention relates generally to the mass spectroscopic analysis of
chemical samples and more particularly to mass spectrometry.
Specifically, an apparatus and method are described for the
transport of ions within and between pressure regions within a mass
spectrometer. Reference is herein made to the figures, wherein the
numerals representing particular parts are consistently used
throughout the figures and accompanying discussion.
[0074] With reference first to FIGS. 7A-C, shown is a plain view of
"segmented" electrode 101 according to the present invention. More
particularly, FIG. 7B shows a cross-sectional view formed at line
A-A in FIG. 7A. FIG. 7C shows a cross-sectional view formed at line
B-B in FIG. 7A. In the preferred embodiment, segmented electrode
101 includes ring-shaped electrically insulating support 115 having
aperture 119 through which ions may pass. Four separate
electrically conducting elements 101a-101d are formed on support
115 by, for example, bonding metal foils to support 115.
Importantly, elements 101a-101d cover the inner rim 119a of
aperture 119 as well as the front and back surfaces of support 115
such that ions passing through aperture 119, will in no event
encounter an electrically insulating surface. Notice also slots
151a-151d formed in support 115 between elements 101a-101d. Slots
151a-151d serve not only to separate elements 101a-101d but also
removes insulating material of support 115 from the vicinity of
ions passing through aperture 119. The diameter of aperture 119,
the thickness of segmented electrode 101, and the width and depth
of slots 151a-151d may all be varied for optimal performance.
However, in this example, the diameter of aperture 119 is 26 mm,
the thickness of electrode 101 is 1.6 mm, and the width and depth
of slots 151 are 1.6 mm and 3.8 mm, respectively.
[0075] Further, while the segmented electrode 101 shown in FIGS.
7A-C depicts the preferred embodiment of segmented electrode 101 as
comprising four conducting elements 101a-101d, alternate
embodiments may be configured with any number of electrically
conducting elements more than one, such as two, six, or eight
elements. For example, as shown in FIGS. 7D-F, segmented electrode
101' includes ring-shaped electrically insulating support 115'
having aperture 119' through which ions may pass. Here, though, six
separate electrically conducting elements 101a'-101f are formed on
support 115'. Importantly, elements 101a'-101f cover the inner rim
of aperture 119' as well as the front and back surfaces of support
115' such that ions passing through aperture 119', will in no event
encounter an electrically insulating surface. Here too, slots are
provided in support 115' between each of elements 101a'-101f' to
both separate elements 101a'-101f' from each other, and remove
insulating material of support 115' from the vicinity of ions
passing through aperture 119'. The diameter of aperture 119', the
thickness of segmented electrode 101', and the width and depth of
the slots may all be varied as discussed above.
[0076] Turning next to FIGS. 8A-B, shown is an end view of a set of
segmented electrodes 101-111 assembled into ion guide 152 according
to the preferred embodiment of the present invention. FIG. 8B shows
a cross-sectional view formed at line A-A in FIG. 8A, which depicts
segmented electrodes 101 through 111 assembled about a common axis
153. In the preferred embodiment of ion guide 152, the distance
between adjacent electrodes 101-111 is approximately equal to the
thickness of the electrodes--in this case 1.6 mm. Also, the
diameter of the apertures in the electrodes 101-111 is a function
of the position of the electrode in ion guide assembly 152. For
example, as depicted in FIG. 8B, the segmented electrode having the
largest aperture (in this example segmented electrode 101) is at
the entrance end 165 of the ion guide assembly 152 and the
segmented electrode having the smallest aperture (in this example
segmented electrode 111) is at the exit end 167 of the ion guide
assembly 152. The aperture diameter in the preferred embodiment is
a linear function of the segmented electrode's position in ion
guide assembly 152. However, in alternate embodiments this function
may be non-linear. Further, in the preferred embodiment, the angle
.alpha. formed between common axis 153 and the inner boundary
(i.e., formed by the inner rims 119a of the segmented electrodes
101-111) of the ion guide assembly 152 is approximately 19.degree..
However, alternatively, any angle between 0.degree. and 90.degree.
may be used.
[0077] Further, each segmented electrode 101-111 in ion guide
assembly 152 consists of four conducting elements a-d. Within any
given segmented electrode 101-111, element a is in electrical
contact with element c and element b is in electrical contact with
element d. That is, element 101a is electrically connected to
element 10c, element 101b is electrically connected to element
101d, element 102a is electrically connected to element 102c, and
so forth.
[0078] As shown in FIGS. 9A-B, the preferred embodiment of ion
guide 152 comprises resistor and capacitor networks (R-C networks)
to provide the electrical connection of all the elements of
segmented electrodes 101-111 to power sources. FIG. 9A depicts a
cross-sectional view of assembly 152 as formed at line A-A in FIG.
8A. Similarly, FIG. 9B depicts a cross-sectional view of assembly
152 as formed at line B-B in FIG. 8A. In the preferred embodiment,
potentials which vary in a sinusoidal manner with time are applied
to the electrodes. A first such sinusoidally varying potential is
applied at +RF and a second sinusoidally varying potential of the
same amplitude and frequency, but 180.degree. out of phase, is
applied at -RF.
[0079] FIG. 9A, the electrical connections for the application of
the +RF 250 and -RF 251 potentials to electrodes 101a-111a and
101c-111c through capacitors 154 is shown. Similarly, electrostatic
potentials +DC 254 and -DC 255 are applied to electrodes 101a-111a
and 101c-111c via resistor divider 157. Similarly, FIG. 9B depicts
the electrical connections for the application of the +RF 252 and
-RF 253 potentials to electrodes 101b-111b and 101d-111d through
capacitors 155, and the electrical connections for the application
of electrostatic potentials +DC 256 and -DC 257 to electrodes
111b-111b and 111d-111d via resistor divider 159. In the preferred
embodiment, capacitors 154 and 155 have the same values such that
the amplitude of the RF potentials 250, 251, 252 and 253 applied to
each of the electrodes 101a-111a, 101b-111b, 101c-111c, and
101d-111d of the segmented electrodes 101-111 in the ion guide
assembly 152 is the same. Also, the resistor dividers 157 and 159
preferably have the same values such that the DC potential is the
same on each element a-d of a given segmented electrode
101-111.
[0080] As an example, the amplitude of the RF potential applied to
+RF and -RF may be 500 Vpp with a frequency of about 1 MHz. The DC
potential applied between +DC and -DC may be 100 V. The capacitance
of capacitors 154 and 155 may be 1 nF. And the resistance of the
resistors in dividers 157 and 159 may be 10 Mohm each. Notice that
for the ions being transmitted the DC potential most repulsive to
the ions is applied to segmented electrode 101 (i.e., at the
entrance end 165 of ion guide 152) while the most attractive DC
potential is applied to segmented electrode 111 (i.e., at the exit
end 167 of ion guide 152). Notice also that each electrically
conducting element 101a-111a, 101b-111b, 101c-111c, and 101d-111d
of the segmented electrodes 101-111 has an RF potential applied to
it which is 180.degree. out of phase with the RF potential applied
to its immediately adjacent elements. For example, the RF potential
applied to element 102a is 180.degree. out of phase with elements
101a and 103a on the adjacent segmented electrodes 101 and 103.
Similarly, the same RF potential applied to element 102a is
180.degree. out of phase with elements 102b and 102d as adjacent
electrically conducting elements on the same segmented electrode
102. Application of the RF potentials in this way prevents the
creation of pseudopotential wells which thereby prevents or at
least minimizes the trapping of ions. Pseudopotential wells, as
discussed in the prior art designs of Smith et al. and of Franzen
et al., can result in the loss of ion transmission efficiency or
the m/z range within which ions are transmitted.
[0081] Turning next to FIGS. 10A-B depicted is two separate views
of ion guide assembly 152, according to an alternate embodiment of
the invention, in which DC lens element 161 is provided at outlet
end 171 of ion guide assembly 152. FIG. 10B shows a cross-sectional
view formed at line A-A in FIG. 10A. In the preferred embodiment,
lens element 161 is composed of electrically conducting material.
Alternatively, lens element 161 may comprise an insulator having an
electrically conductive coating. Preferably, lens element 161
includes aperture 163 aligned with axis 153 of ion guide 152. It is
also preferred that aperture 163 be round with a diameter of
approximately 2 mm. However, in alternate embodiments, the aperture
may take any desired shape or size. In practice the DC potential
applied to lens element 161 should be more attractive to the
transmitted ions than segmented electrode 111. As an ion guide, the
present invention has applicability in a variety of ways in a mass
spectrometer system. FIG. 11 depicts the ion guide assembly 161 of
FIG. 10 in the vacuum system of a mass spectrometer. The vacuum
system of the mass spectrometer shown consists, for example, of
four chambers 173, 175, 177 and 179. Although gas pressures in the
chambers may vary widely, examples of gas pressures in a system
such as this are .about.1 mbar in chamber 173,
.about.5.times.10.sup.-2 mbar in chamber 175,
.about.5.times.10.sup.-3 mbar in chamber 177, and
.about.5.times.10.sup.-7 in chamber 179. To achieve and maintain
the desired pressure levels in these chambers, each of chambers
173, 175, 177, and 179 include pumping ports 181, 183, 184, and
185, respectively, through which gas may be pumped away.
[0082] In the embodiment shown, capillary 186 transmits ions and
gas from an atmospheric pressure ion production means 258 into
chamber 173. As indicated previously, such ion production means may
include any known API means including but not limited to ESI,
atmospheric pressure chemical ionization, atmospheric pressure
MALDI, and atmospheric pressure photoionization. Also, other known
prior art devices might be used instead of capillary 186 to
transmit ions from ion production means 258 into first chamber 173.
Once the transmitted ions exit capillary 186 into first chamber
173, ion guide assembly 152, residing in first chamber 173, accepts
the transmitted ions, while gas introduced via capillary 186 is
pumped away via pumping port 181 to maintain the desired pressure
therein. Through the appropriate application of electric potentials
as discussed above with respect to FIGS. 9A-B and 10A-B, ion guide
assembly 152 focuses the transmitted ions from the exit end of the
capillary 186 toward and through aperture 163 of lens element 161
positioned at outlet end 171 of ion guide 152. In addition, lens
element 161 preferably acts as a pumping restriction between first
chamber 173 and second chamber 175.
[0083] Preferably, multipole ion guide 187 resides in second
chamber 175 and multipole ion guide 188 resides in third chamber
177. Ion guide 187 serves to guide ions through chamber 175 toward
and through lens 189, while ion guide 188 similarly serves to guide
ions from lens 189 through chamber 177 toward and through lens 190.
Lenses 189 and 190 may also serve as pumping restrictions between
chambers 175 and 177 and between chambers 177 and 179,
respectively. In addition, lenses 189 and 190 are shown as
electrode plates having an aperture therethrough, but other known
lenses such as skimmers, etc., may be used. Ions passing through
lens 190 into fourth chamber 179 may subsequently be analyzed by
any known type of mass analyzer (not shown) residing in chamber
179.
[0084] Although the potentials applied to the components of the
system shown in FIG. 11 may be varied widely, an example of the DC
electric potentials which may be applied to each component in
operating such a system are: TABLE-US-00001 capillary 186 125 V
segmented electrode 1 120 V segmented electrode 111 20 V lens
element 161 19 V multipole 187 18 V lens element 189 17 V multipole
188 15 V lens element 190 0 V.
[0085] In an alternate embodiment, lens element 161 might be
replaced with a segmented electrode of essentially the same
structure as segmented electrodes 101-111. In such an embodiment,
lens element 161 would preferably be electrically driven in
substantially the same manner as the electrodes 101-111--i.e. RF
and DC potentials--but would additionally act as a pumping
restriction.
[0086] In the preferred embodiment of FIG. 11, the multipoles 187
and 188 are hexapoles, however in alternate embodiments they might
be any type of multipole ion guide--e.g quadrupole, octapole, etc.
The RF potential applied to the rods of multipoles 187 and 188 may
also vary widely, however one might apply a sinusoidally varying
potential having an amplitude of 600 Vpp and frequency of 5
MHz.
[0087] In an alternate embodiment, multipole 188 might be a
quadrupole. Further, as is known in the prior art, one might use
multipole 188 to select and fragment ions of interest before
transmitting them to chamber 179.
[0088] Turning next to FIG. 12, a two-stage ion guide 199 according
to yet another alternate embodiment of the invention is depicted.
As shown, two-stage ion guide 199 incorporates ion guide assembly
152 of FIGS. 10A-B with a second ion guide 201 comprising
additional segmented electrodes 191-195 and DC lens 197. In this
embodiment, ion guide assembly 152 acts as the first stage of
two-stage ion guide 199, with the additional segmented electrodes
191-195 and lens 197 forming second stage 201 of the two-stage ion
guide 199. As depicted, all of the segmented electrodes 101-111 and
191-195 and lenses 161 and 197 are aligned on common axis 153.
While the angle .beta. formed between the common axis 153 and the
inner boundary (i.e., formed by the inner, rims of the segmented
electrodes 191-195) of the second stage 201 of two-stage ion guide
199 is independent from angle .alpha. of first stage ion guide
assembly 169 (the angle .alpha. is discussed above in regard to
FIGS. 8A-B), these angles .alpha. and .beta. are preferably the
same. Similarly, the thickness and spacing between segmented
electrodes 191-195 are preferably the same as the thickness of and
spacing between segmented electrodes 101-111, as discussed above.
Also, it is preferred that lens 197 is electrically conducting with
a 2 millimeter (mm) diameter aperture aligned on axis 153. The RF
potentials applied to the electrically conducting elements of
segmented electrodes 191-195 are preferably of the same amplitude
and frequency as that applied in first stage ion guide assembly
152. The DC potentials applied to segmented electrodes 191-195 are
such that ions are repelled from lens 161 and attracted toward lens
197.
[0089] Like FIG. 11, FIG. 13 depicts an ion guide according to the
invention as it may be used in a mass spectrometer. Specifically,
FIG. 13 depicts the two-stage ion guide 199 of FIG. 12 positioned
in the vacuum system of a mass spectrometer. The system depicted in
FIG. 13 is the same as that of FIG. 11 with the exception that ion
guide 187 and lens 189 shown in FIG. 11 are replaced with second
stage ion guide 201 in FIG. 13 which includes ion lens 197. As
depicted in FIG. 13, two stage ion guide 199 is capable of
accepting and focusing ions even at a relatively high pressure
(i.e., .about.1 mbar in first pumping chamber 173) and can
efficiently transmit them through a second, relatively low pressure
differential pumping stage (i.e., .about.5.times.10.sup.-2 mbar in
second pumping chamber 175) and into a third pumping chamber 177.
Notice that although lenses 161 and 197 are shown to be integrated
into two-stage ion guide 199, they also act as pumping restrictions
between chambers 173 and 175, and between 175 and 177,
respectively. The ability of two-stage ion guide 199, as a single
device, to efficiently guide and transmit ions over a wide range of
pressure regions and through a plurality of pumping stages is one
of the principle advantages of the present invention over prior art
ion guides.
[0090] In an alternate embodiment, lens element 161 might be
replaced with a segmented electrode of essentially the same
structure as segmented electrodes 101-111. In such an embodiment,
lens element 161 would preferably be electrically driven in
substantially the same manner as the electrodes 101-111--i.e. RF
and DC potentials, but would additionally act as a pumping
restriction.
[0091] In a further alternate embodiment, lens element 197 might
also be replaced with a segmented electrode of essentially the same
structure as segmented electrodes 101-111 and 191-195. In such an
embodiment, lens element 197 would preferably be electrically
driven in substantially the same manner as the electrodes 101-111
and 191-195--i.e. RF and DC potentials--but would additionally act
as a pumping restriction.
[0092] Referring now to FIG. 14, depicted is a "stacked ring" ion
guide 202 according to yet another alternate embodiment of the
present invention. As shown, stacked ring ion guide 202 includes
"DC electrodes" 203 interleaved with RF guide rings 204a and 204b.
Preferably, RF guide rings 204 are apertured plates preferably
composed of electrically conducting material (e.g., metal). The
dimensions and placement of RF guide rings 204 may vary widely.
However, it is preferred that RF guide rings 204a and 204b be
approximately 1.6 mm thick, have apertures 208 which are
approximately 6 mm in diameter, and be positioned with spacing
between adjacent RF guide rings 204a and 204b of 1.6 mm. Also,
rings 204a and 204b are preferably aligned along common axis 205.
As shown, this embodiment includes apertured lens elements 206 and
207 positioned at either end of stacked ring ion guide 202 and are
also aligned along axis 205. Lenses 206 and 207 are preferably
electrically conducting plates with approximately 2 mm diameter
apertures.
[0093] Stacked ring ion guide 202 also comprises DC electrodes 203
which are thin (e.g., .about.0.1 mm) electrically conducting plates
positioned midway between adjacent RF guide rings 204a and 204b and
have apertures 209 with preferably the same diameter as apertures
208 in RF guide rings 204a and 204b.
[0094] During operation, sinusoidally time-varying potentials
RF.sub.3 are applied to RF guide rings 204. Preferably a first
time-varying potential +RF.sub.3 is applied to ring 204a, and a
second time-varying potential -RF.sub.3 is applied to rings RF
guide 204b. Potentials +RF.sub.3 and -RF.sub.3 are preferably of
the same amplitude and frequency but are 180.degree. out of phase
with one another. Also, the potentials +RF.sub.3 and -RF.sub.3 may
have a non-zero reference potential such that the entire stacked
ring ion guide 202 has a "DC offset" of, for example, 15V.
Potentials are applied to DC electrodes 203 via RC network 210. In
the preferred method of operation, the inputs TNL1 and TNL2 to RC
network 210 are maintained at the same electrostatic potential as
the DC offset of stacked ring ion guide 202 as a whole.
Alternatively, to trap ions in the ion guide, one can set the DC
potentials on lenses 206 and 207 to some potential above the DC
offset of the remainder of stacked ring ion guide 202.
[0095] FIG. 15 shows a plot of electric potential vs. position
within stacked ring ion guide 202. In particular, trace 211 of FIG.
15 is a plot of the electrostatic potential on axis 205 of ion
guide 202 when operated in the manner described above to trap ions.
One may operate stacked ring ion guide 202 in this manner to
accumulate ions within stacked ring ion guide 202. Ions may be
introduced into stacked ring ion guide 202 from an ion production
means via aperture 213 in lens 206 (see FIG. 14). Ions may then
undergo collisions with a gas in stacked ring ion guide 202 thus
losing kinetic energy and becoming trapped. The efficiency of
trapping ions in this manner is dependent on the gas pressure and
composition within stacked ring ion guide 202.
[0096] Once ions are trapped in stacked ring ion guide 202, the
electrostatic potential along axis 205 may be changed so as to
eject ions from stacked ring ion guide 202. Trace 212 of FIG. 15
shows the electrostatic potential as a function of position along
axis 205 when the potential at TNL2 (see FIG. 14) is lowered to
only a few volts and potential L2 (see FIG. 14) applied to lens 207
is lowered to 0V. The gradient in the electrostatic potential along
axis 205 will tend to eject ions from guide 202 through aperture
214 in lens 207.
[0097] When operated in the preferred manner, the potential on the
elements 203 of stacked ring ion guide 202 are maintained for a
predetermined time so as to accumulate and trap ions from an ion
production means in stacked ring ion guide 202. After this
predetermined time, however, the potentials TNL2 and L2 are rapidly
pulsed to lower potentials so as to quickly eject ions from stacked
ring ion guide 202. In the preferred method, the transition of the
potentials TNL2 and L2 is on the same order of or faster than the
frequency of the RF potential applied at RF.sub.3. Notice that,
unlike the prior art ion guide of Franzen et aL discussed above,
the formation of an electrostatic field along the axis of stacked
ring ion guide 202 does not require the application of a DC
potential gradient to RF guide rings 204a and 204b. Rather, the
electrostatic field is formed via DC electrodes 203 independent of
RF guide rings 204a and 204b. As a result, the electrostatic
gradient represented by trace 212 can be generated as rapidly as
necessary without considering the frequency at which RF guide rings
204a and 204b are being driven. As an example, potentials +RF.sub.3
and -RF.sub.3 may be 500 Vpp at 1 MHz, ions may be accumulated for
10 msec from an ESI source. Thereafter, the potentials TNL2 and L2
can be lowered to 4 V and 0 V respectively in a pulsed manner with
a fall time of 100 ns and a duration of 100 .mu.sec. After the
duration of 100 .mu.sec, the potentials TNL2 and L2 can be raised
to their trapping potentials of 15 V and 25 V, respectively, and
the process may be repeated. The pulses of ions thus produced are
injected into a mass analyzer residing "downstream" from stacked
ring ion guide 202.
[0098] Turning next to FIG. 16, shown is yet another alternative
embodiment of an ion guide according to the present invention. As
shown, this embodiment comprises features of both ion funnel 152
(FIGS. 8A-B) and stacked ring ion guide 202 (FIG. 14).
Specifically, ion guide 220 of FIG. 16 is the same as ion guide 202
with the addition of guide rings 216-219, capacitors 215, and
resistor divider 221. In this embodiment, guide rings 216-219 act
as a funnel-like ion guide as describe above. The thickness and
spacing between guide rings 216-219 may vary widely. However, the
thickness of electrodes 216-219 is preferably the same as that of
rings 204a and 204b (e.g., 1.6 mm) and the spacing between
electrodes 216-219 is preferably the same as that between
electrodes 204a and 204b (e.g. 1.6 mm). Also, the angle .gamma.
formed between common axis 205 of ion guide 220 and the inner
boundary ring electrodes 216-219 may vary widely. However, it is
shown here to be 190. The RF potential on guide rings 216-219 is
set by RF.sub.3 and -RF.sub.3 through capacitors 215 as described
above. In the preferred method of operation, the RF potential
applied to guide rings 216-219 is the same as that applied to RF
rings 204a and 204b. However, in alternate embodiments, the RF
potential applied to rings 216-219 might be of a different
amplitude or frequency than that applied to rings 204a and 204b.
The DC potentials on rings 216-219 are applied via resistor divider
221. Also in the preferred method of operation, the potentials FNL1
and FNL2 applied to resistor divider 221 are such that ions are
accelerated along axis 205 toward the exit end of the ion guide 220
at lens 207. Also, in the preferred method of operation, the DC
potential on ring 219 should be approximately the same or slightly
higher than that on electrodes 204a and 204b, as represented in
traces 222 and 223 in FIG. 17.
[0099] Similar to FIG. 15, FIG. 17 plots the electrostatic
potential as a function of position in ion guide 220 on axis 205.
First, trace 222 of FIG. 17 is a plot of the electrostatic
potential on axis 205 of ion guide 220 when operated to trap ions.
One may operate in this manner to accumulate ions in ion guide 220.
Ions may be introduced into guide 220 from an ion production means
via aperture 213 in lens 206 (see FIG. 16). Ions may then undergo
collisions with a gas in guide 220 thus losing kinetic energy and
becoming trapped. The efficiency of trapping ions in this manner is
dependent on the gas pressure and composition in ion guide 220.
[0100] Once ions are trapped in ion guide 220, the electrostatic
potential along axis 205 may be changed so as to eject ions from
ion guide 220. Trace 223 of FIG. 17 shows the electrostatic
potential as a function of position along axis 205 when the
potential at TNL2 (see FIG. 16) is lowered to only a few volts and
potential L2 (see FIG. 16) applied to lens 207 is lowered to 0V.
The gradient in the electrostatic potential along axis 205 will
tend to eject ions from guide 220 through aperture 214 in lens
207.
[0101] When operated in the preferred manner, the potential on the
elements 203 of ion guide 220 are maintained for a predetermined
time so as to accumulate and trap ions from an ion production means
in ion guide 220. After this predetermined time, however, the
potentials TNL2 and L2 are rapidly pulsed to lower potentials so as
to quickly eject ions from ion guide 220. In the preferred method,
the transition of the potentials TNL2 and L2 is on the same order
of or faster than the frequency of the RF potential applied at
RF.sub.3. Notice that, unlike the prior art ion guide of Franzen et
al. discussed above, the formation of an electrostatic field along
the axis of ion guide 220 does not require the application of a DC
potential gradient to RF guide rings 204a and 204b. Rather, the
electrostatic field is formed via DC electrodes 203 independent of
RF guide rings 204a and 204b. As a result, the electrostatic
gradient represented by trace 223 can be generated as rapidly as
necessary without considering the frequency at which RF guide rings
204a and 204b are being driven. As an example, potentials +RF.sub.3
and -RF.sub.3 may be 500 Vpp at 1 MHz, and ions may be accumulated
for 10 msec from an ESI source. Thereafter, the potentials TNL2 and
L2 can be lowered to 4 V and 0 V respectively in a pulsed manner
with a fall time of 100 ns and a duration of 100 .mu.sec. After the
duration of 100 .mu.sec, the potentials TNL2 and L2 may be raised
to their trapping potentials of 15 V and 25 V, respectively, and
the process may be repeated. The pulses of ions thus produced are
injected into a mass analyzer residing "downstream" from ion guide
220.
[0102] While electrodes 204a and 204b of ion guides 202 and 220
have been described as ring electrodes, in an alternative
embodiment of those ion guides according to the invention,
electrodes 204a and 204b may further be segmented electrodes as
described with reference to FIG. 7. Such a stacked ring ion guide
with segmented electrodes is depicted in FIG. 18.
[0103] FIG. 18 further depicts two-stage ion guide 199 used in
conjunction with stacked ring ion guide 224, assembled together in
the vacuum system of a mass spectrometer. The system depicted in
FIG. 18 is identical to that of FIG. 13 with the exception of the
replacement of ion guide 188 in FIG. 13 with stacked ring ion guide
224 in FIG. 18. As depicted in FIG. 18, two stage ion guide 199 can
accept ions and focus them even at a relatively high pressure
(i.e., in first pumping stage 173) and can efficiently transmit
them through a second, relatively low pressure, differential
pumping stage (i.e., chamber 175) to third chamber 177. With the
addition of ion guide 224, the assembly has the advantage over
prior art that ions can be trapped and rapidly ejected into chamber
179 and the mass analyzer residing therein. In alternate
embodiments, ion guide 224 might extend through multiple pumping
stages. In such a system, one or more of the electrodes 204 might
also serve as pumping restrictions.
[0104] Referring to FIGS. 19A-B shown are the electrical
connections for ion guide 225 of FIG. 18. Specifically, FIG. 19A
shows a first cross-sectional depiction of the electrical
connections to ion guide 225 according to the present invention as
depicted in FIG. 18. Next, FIG. 19B shows a second cross-sectional
depiction, orthogonal to that of FIG. 19A, of the electrical
connection to ion guide 225. As shown, ion guide 225 is
electrically connected in a manner similar to that described above
with respect to FIGS. 9, 14, and 16. In this embodiment, capacitors
154, 155, 215, 226, 228, and 230 all preferably have the same
capacitance. Alternatively, the capacitance of capacitors 154 and
155 may differ from the capacitance of capacitors 226 and 228, as
well as from that of capacitors 215 and 230. Similarly, resistors
157, 159, 221, 227, 229, and 231 are all preferably identical.
However, in alternate embodiments, the resistance of these
resistors may differ from one another. Also, in this embodiment, it
is preferred that the RF potentials applied at RF.sub.1, RF.sub.2,
and RF.sub.3 be identical to one another. However, in alternate
embodiments, the RF frequencies and/or amplitudes applied at inputs
RF.sub.1, RF.sub.2, and RF.sub.3 may differ from one another.
Finally, it is preferred that the various DC potentials applied to
the electrodes are such that the ions being transmitted are
attracted toward the exit end of ion guide 225 and analyzer chamber
179. As discussed above, however, the inputs TNL1 and TNL2 of RC
network 210 may be biased such that ions are either trapped in or
ejected from that portion of ion guide 225.
[0105] Yet another alternative embodiment of the present invention
is shown in FIG. 20. In particular, shown are ion guides 199 and
224 positioned in the vacuum system of a mass spectrometer with two
multipole ion guides 188 and 232 positioned there between. In the
embodiment depicted in FIG. 20, the pressures in vacuum chambers
173, 175, and 177 and the operation of elements 186, 199, and 188
are substantially similar to that described with reference to FIG.
13. According to this embodiment, multipole ion guide 188 is a
hexapole and multipole ion guide 232 is a quadrupole. As described
above, an RF-only potential is applied to hexapole ion guide 188 so
as to guide ions through chamber 177 and into chamber 179.
[0106] Preferably, chamber 179 is operated at a pressure of
10.sup.-5 mbar or less such that quadrupole 232 may be used to
select ions of interest. It is also preferable that quadrupole 232
be used either to transmit substantially all ions or only selected
ions through chamber 179 into chamber 233 and ion guide 224
positioned therein. As is well known from the prior art,
substantially all ions will be transmitted through quadrupole 232
when an RF-only potential is applied to it. To select ions of
interest, both RF and DC potentials must be applied.
[0107] Similar to that described above, selected ions are
accelerated into chamber 233 and ion guide 224 via an electric
field. The gas pressure of chamber 233 is preferably 10.sup.-3 mbar
or greater. Typically the gas used is inert (e.g., Nitrogen or
Argon) however, reactive species might also be introduced into the
chamber. When the potential difference between ion guides 232 and
224 is low, for example 5V, the ions are simply transmitted
therethrough. That is, the ions will collide with the gas in ion
guide 224, but the energy of the collisions will be low enough that
the ions will not fragment. However, if the potential difference
between ion guides 232 and 224 is high, for example 100 V, the
collisions between the ions and gas may cause the ions to
fragment.
[0108] In this manner ion guide 224 may act as a "collision cell".
However, unlike prior art collision cells, the funnel-like entrance
of ion guide 224 allow for the more efficient capture of the
selected "precursor" and "fragment" ions. Precursor and fragment
ions may be trapped in the manner described above with reference to
FIGS. 16 and 17. Through collisions with the gas, the ions may be
cooled to the temperature of the collision gas, typically room
temperature. These ions will eventually be ejected from ion guide
224 into chamber 234 where an additional mass analyzer (not shown)
may be used to analyze both the precursor and fragment ions and
produce precursor and fragment ion spectra. In alternate
embodiments, any of the other ion guides disclosed herein, for
example ion guide 152 shown in FIG. 10B, may be substituted for ion
guide 224.
[0109] The mass analyzer in chamber 234 may be any type of mass
analyzer including but not limited to a time-of-flight, ion
cyclotron resonance, linear quadrupole or quadrupole ion trap mass
analyzer. Further, any type of mass analyzer might be substituted
for quadrupole 232. For example, a quadrupole ion trap (i.e., a
Paul trap), a magnetic or electric sector, or a time-of-flight mass
analyzer might be substituted for quadrupole 232.
[0110] Still referring to FIG. 20, while trapped in ion guide 224
the ions may be further manipulated. For example, as discussed by
Hofstadler et al., an ion guide may operate at a predetermined
pressure such that ions within such ion guide may be irradiated
with light and thereby caused to form fragment ions for subsequent
mass analysis. Selected ions are preferably collected in the ion
guide 224 in a generally mass-inselective manner. This permits
dissociation over a broad mass range, with efficient retention of
fragment ions. In the embodiments of the present invention
disclosed herein, it is preferred that the pressure in chamber 233
be relatively high (e.g., on the order of 10.sup.3-10.sup.6 mbar).
Irradiating ions in such a high pressure region results in two
distinct advantages over traditional Infrared Multiphoton
Dissociation (IRMPD) as exemplified in Fourier Transform Ion
Resonance (FTICR) and Quadrupole Ion Trap (QIT) mass spectrometry.
Under high pressures, collisions with neutrals will dampen the ion
cloud to the center of ion guide 224 and stabilize fragment ions,
resulting in significantly improved fragment ion retention. In
addition, the fragment ion coverage is significantly improved,
providing more sequence information.
[0111] Alternatively, ions might be activated toward fragmentation
by oscillating the potentials on TNL1 and TNL2 (see RC network
shown and described in reference to FIG. 16). As depicted in FIG.
21, ions may be accelerated back and forth within ion guide 224.
When the potential applied at TNL1 (i.e., at lens 206) is held high
relative to the potential applied at TNL2 (i.e., at lens 207) ions
will be accelerated toward the exit end of ion guide 224 (i.e.,
toward chamber 234). As indicated by trace 237, the ions are
prevented from escaping ion 224 by the RF on electrodes 204a and
204b and the repelling DC potential on lens electrode 207.
Reversing the potentials applied at TNL1 and TNL2 results in a
potential along the common axis of ion guide 224 represented by
trace 238. The ions are then accelerated away from the exit end of
ion guide 224 (i.e., at lens 207). In this situation, the ions are
prevented from escaping ion guide 224 again by the RF potential on
electrodes 204a and 204b and the repelling DC potentials on lens
electrode 206 and ring electrodes 216-219. By rapidly alternating
the forward and reverse acceleration of ions in guide 224 (i.e., by
reversing the potentials applied at TNL1 and TNL2), the ions are
caused to repeatedly undergo collisions with gas within ion guide
224. This tends to activate the ions toward fragmentation. At some
predetermined time, the potentials on guide 224 will be brought
back to that represented by trace 222 (seen in FIG. 17). At that
time the ions will be cooled via collisions with the gas to the
temperature of the gas. Then the ions will be ejected from ion
guide 224 by applying potentials represented by trace 223 (seen in
FIG. 17).
[0112] Turning now to FIG. 22, depicted is a system according to
another embodiment of the present invention wherein an ion guide
according to one or more of the embodiments disclosed herein (e.g.,
ion guide 225 seen in FIG. 18) may be used with an orthogonal ion
production means. That is, axis 240 of inlet orifice or capillary
186 is oriented so as to introduce ions orthogonal to axis 153 of
ion guide 225. As discussed above, gas and ions are introduced
from, for example, an elevated pressure ion production means (not
shown) into chamber 173 via an inlet orifice or capillary 186.
After exiting orifice or capillary 186 the directional flow of the
ions and gas will tend to follow axis 240. Preferably, pumping port
181 is coaxial with inlet orifice or capillary 186 so that the gas,
entrained particulates and droplets will tend to pass directly to
port 181 and the corresponding pump. This is a significant
advantage in that electrode 239 and ion guide 225 will not readily
become contaminated with these particulates and droplets.
[0113] In this embodiment, electrode 239 is preferably a planar,
electrically conducting electrode oriented perpendicular to axis
153. A repulsive potential is applied to electrode 239 so that ions
exiting orifice or capillary 186 are directed toward and into the
inlet of ion guide 225. The distances between potentials applied to
elements 186, 239, and 225 may vary widely, however, as an example,
the distance between axis 153 and orifice 186 in is preferably 13
mm, the lateral distance between axis 240 and the entrance of ion
guide 225 is preferably 6 mm, and the distance between electrode
239 and the entrance of ion guide 225 is preferably 12 mm. The DC
potentials on electrodes 101, 186, and 239 may be 100 V, 200 V, and
200 V respectively, when analyzing positive ions. As shown, angle
.alpha. is 90.degree. (i.e., orthogonal), but in alternate
embodiments the angle .alpha. need not be 90.degree. but may be any
angle.
[0114] Referring finally to FIG. 23, shown is the system depicted
in FIG. 22 wherein electrode 239 is used as a sample carrier for a
Matrix-Assisted Laser Desorption/Ionization (MALDI) ion production
means. In this embodiment, electrode 239 may be removable or partly
removable from the system via, for example, a vacuum interlock (not
shown) to allow replacement of the sample carrier without shutting
down the entire vacuum system. At atmospheric pressure, separate
from the rest of the system, MALDI samples are applied to the
surface of electrode 239 according to well known prior art methods.
Electrode 239 now with samples deposited thereon (not shown) is
introduced into the system via the above-mentioned vacuum interlock
so that it comes to rest in a predetermined position as depicted in
FIG. 23. Electrode 239 may reside on a "stage" which moves
electrode 239 in the plane perpendicular to axis 153.
[0115] In this embodiment, window 242 is incorporated into the wall
of chamber 173 such that laser beam 241 from a laser positioned
outside the vacuum system may be focused onto the surface of
electrode 239 such that the sample thereon is desorbed and ionized.
On the sample carrier electrode 239, the sample being analyzed will
reside approximately at axis 153. However, a multitude of samples
may be deposited on the electrode 239, and as each sample is
analyzed, the position of electrode 239 is change via the
above-mentioned stage such that the next sample to be analyzed is
moved onto axis 153. For this embodiment, any prior art laser,
MALDI sample preparation method, and MALDI sample analysis method
might be used.
[0116] During the MALDI analysis as described above, inlet orifice
or capillary 186 may be plugged so that no gas, or alternatively a
reduced flow of gas, enters chamber 173. Alternatively, one may
produce ions simultaneously via a multitude of ion production
means. For example, one might introduce ions from an electrospray
ion production means via orifice 186 while simultaneously producing
MALDI ions from samples on electrode 239. Though not shown, more
than two ion production means might be used in this manner either
consecutively or simultaneously to introduce ions into ion guide
225.
[0117] While the present invention has been described with
reference to one or more preferred and alternate embodiments, such
embodiments are merely exemplary and are not intended to be
limiting or represent an exhaustive enumeration of all aspects of
the invention. The scope of the invention, therefore, shall be
defined solely by the following claims. Further, it will be
apparent to those of skill in the art that numerous changes may be
made in such details without departing from the spirit and the
principles of the invention. It should be appreciated that the
present invention is capable of being embodied in other forms
without departing from its essential characteristics.
* * * * *